The present invention is directed to the production of novel compositions, useful as vaccines for treating white blood cell (WBC) malignancies. The invention relates to a liposomal, patient-specific vaccine comprised of WBC membranes that may be formulated by adding other lipids and/or immunostimulators, thereby forming a novel membrane-proteoliposome (MP) structure.
Known vaccines typically utilize either purified antigen or attenuated pathogen as the immunogen. However, attenuated vaccines can actually cause the infection against which a person is being immunized. On the other hand, purified antigens may not induce a longterm immune response and sometimes induce no response at all. In contrast to the short-term immune response obtained by direct immunization with certain antigens, presentation of the antigen in the presence of liposomes can induce a long-term response which is essential for any effective vaccine.
Although typically formed from purified or partially purified lipids, liposomes may also be formed, at least in part, from cell membranes of malignant cells which contain potential antigens. Due to the presence of membrane associated antigens, these membranederived preparations may be used as malignancy-specific vaccines. Indeed, some types of membrane-derived preparations have been used as tumor specific antigens (TSA) to treat melanomas and murine SL2 lymphosarcoma. See Gershman et al., Vaccine Res. 3:83-92 (1994); Bergers et al., J. Confr. Rel. 29:317-27 (1994); Bergers et al., J. Liposome Res. 6:339-35 (1996). In these cases, the production of vaccine suffered from serious disadvantages. Namely, they required pooling culture adapted cells to achieve large amounts of the desired cell populations, use of whole .gamma.-irradiated tumor cells, detergent solubilization or butanol for crude extraction of tumor-associated antigens (TAA). See Gershman et al. (1994), supra; Abbas, et al., CELLULAR AND MOLECULAR IMMUNOLOGY, pp.372-73 (W. B. Saunders Company, Philadelphia 1994); Bergers et al. (1994), supra; LeGrue et al., J. Natl. Cancer Inst. 65:191-96 (1980). This approach, moreover, is not patient-specific.
The art is also aware of some vaccines directed to certain B cell malignancies. Typically, however, attempts at producing vaccines for B-cell lymphoma have relied on the costly and time consuming hybridoma technology. These methods depend on generating a hybridoma able to produce the tumor-specific immunoglobulin (Ig) in enough quantity to be then used as a vaccine. Kwak et al., Blood 76:2411-17 (1990); Kwak et al., N. Engl. J. Med. 327:1209-15 (1992). Known B-cell lymphoma vaccines employ Ig idiotype (Id) to generate anti-idiotype antibodies to B-cells. Levy et al., PCT/US94/08601 (Feb. 23, 1995); Levy et al., U.S. Pat. No. 4,816,249 (1989). Similarly, known melanoma vaccines involved harvesting cell surface antigens which are shed during culturing. Bystryn, U.S. Pat. No. 5,635,188 (1997); Bystryn, U.S. Pat. No. 5,194,384 (1993); Bystryn, U.S. Pat. No. 5,030,621 (1991).
There is, therefore, an unmet need in the art for improved liposome-based vaccines. A particular need exists for improved vaccines against white blood cell malignancies.